Effective therapy for human immunodeficiency virus (HIV) infection remains elusive, partly dueto the fact that infected long lived cells provide a reservoir for the virus. Currently availableanti-retroviral agents are reverse transcriptase inhibitors. In spite of their success, these compoundshave limited utility because their toxicity and lack of action have no effect on the production ofinfectious virus in cells harboring integrated provirus. Therefore, it is important to alternative approacheswhich target other factors important to the life cycle of the virus. This approach would involve targetingcompounds which interfere with the viral integrate enzyme in the HIV life cycle. Development ofclinically tolerable inhibitors of HIV integrate would have profound implications for anti- retroviral therapyby offering a wide range of application including potential synergy with the currently available reversetranscriptase inhibitors in acute HIV infections and as agents to target HIV-1 in chronically infected cells.We will design inhibitors targeted to HIV integrate and evaluate their therapeutic utility using in vitroassay systems. The promising compounds will further be evaluated in tissue culture and in vivo assaysystems.